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BIO-MEDICAL INSTRUMENTATION (UEI608) Lecture: Problems encountered in measuring a By living system Dr. Deepti Mittal (Associate Professor) Department of Electrical & Ins...

BIO-MEDICAL INSTRUMENTATION (UEI608) Lecture: Problems encountered in measuring a By living system Dr. Deepti Mittal (Associate Professor) Department of Electrical & Instrumentation Engineering Thapar Institute of Engineering & Technology Patiala, India PROBLEMS ENCOUNTERED IN MEASURING A LIVING SYSTEM The previous discussions of the man-instrument system and the physiological systems of the body imply measurements on a human subject. In some cases, however, animal subjects are substituted for humans in order to permit measurements or manipulations that cannot be performed without some risk. Although ethical restrictions sometimes are not as severe with animal subjects, the same basic problems can be expected in attempting measurements from any living system. However, they can be summarized as follows. Inaccessibility of Variables to Measurement One of the greatest problems in attempting measurements from a living system is the difficulty in gaining access to the variable being measured. In some cases, such as in the measurement of dynamic neurochemical activity in the brain, it is impossible to place a suitable transducer in a position to make the measurement. Sometimes the problem stems from the required physical size of the transducer as compared to the space available for the measurement. In other situations the medical operation required to place a transducer in a position from which the variable can be measured makes the measurement impractical on human subjects, and sometimes even on animals. Where a variable is inaccessible for measurement, an attempt is often made to perform an indirect measurement. This process involves the measurement of some other related variable that makes possible a usable estimate of the inaccessible variable under certain conditions. In using indirect measurements, however, one must be constantly aware of the limitations of the substitute variable and must be able to determine when the relationship is not valid. Variability of the Data Few of the variables that can be measured in the human body are truly deterministic variables. In fact, such variables should be considered as stochastic processes. A stochastic process is a time variable related to other variables in a nondeterministic way. Physiological variables can never be viewed as strictly deterministic values but must be represented by some kind of statistical or probabilistic distribution. In other words, measurements taken under a fixed set of conditions at one time will not necessarily be the same as similar measurements made under the same conditions at another time. The variability from one subject to another is even greater. Here, again, statistical methods must be employed in order to estimate relationships among variables. Lack of Knowledge About interrelationships The foregoing variability in measured values could be better explained if more were known and understood about the interrelationships within the body. Physiological measurements with large tolerances are often accepted by the physician because of a lack of this knowledge and the resultant inability to control variations. Better understanding of physiological relationships would also permit more effective use of indirect measurements as substitutes for inaccessible measures and would aid engineers or technicians in their job of coupling the instrumentation to the physiological system. Interaction Among Physiological Systems Because of the large number of feedback loops involved in the major physiological systems, a severe degree of interaction exists both within a given system and among the major systems. The result is that stimulation of one part of a given system generally affects all other parts of that system in some way (sometimes in an unpredictable fashion) and often affects other systems as well. For this reason, “cause-and-effect" relationships become extremely unclear and difficult to define. Even when attempts are made to open feedback loops, collateral loops appear and some aspects of the original feedback loop are still present. Also, when one organ or element is rendered inactive, another organ or element sometimes takes over the function. Effect of the Transducer on the Measurement Almost any kind of measurement is affected in some way by the presence of the measuring The problem is greatly compounded in the measurement of living systems. transducer. In many situations the physical presence of the transducer changes the reading significantly. For example, a large flow transducer placed in a bloodstream partially blocks the vessel and changes the pressure-flow characteristics of the system. Similarly, an attempt to measure the electrochemical potentials generated within an individual cell requires penetration of the cell by a transducer. This penetration can easily kill the cell or damage it so that it can no longer function normally. Another problem arises from the interaction. Often the presence of a transducer in one system can affect responses in other systems. For example, local cooling of the skin, to estimate the circulation in the area, causes feedback that changes the circulation pattern as a reaction to the cooling. The psychological effect of the measurement can also affect the results Long-term recording techniques for measuring blood pressure have shown that some individuals who would otherwise have normal pressures show an elevated pressure reading whenever they are in the physician's office. This is a fear response on the part of the patient, involving the autonomic nervous system. In designing a measurement system, the biomedical instrumentation engineer or technician must exert extreme care to ensure that the effect of the presence of the measuring device is minimal. Because of the limited amount of energy available in the body for many physiological variables, care must also be taken to prevent the measuring system from “loading'' the source of the measured variable. Loading means source is not able to deliver desired power or voltage to load. Artifacts In medicine and biology, the term artifact refers to any component of a signal that is extraneous to the variable represented by the signal. Thus, random noise generated within the measuring instrument, electrical interference (including 60-Hz pickup), cross-talk, and all other unwanted variations in the signal are considered artifacts. A major source of artifacts in the measuring of a living system is the movement of the subject, which in turn results in movement of the measuring device. Since many transducers are sensitive to movement, the movement of the subject often produces variations in the output signal. Sometimes these variations are in-distinguishable from the measured variable; at other times they may be sufficient to obscure the desired information completely. Application of anesthesia to reduce movement may itself cause unwanted changes in the system. Energy Limitations Many physiological measurement techniques require that a certain amount of energy be applied to the living system in order to obtain a measurement. For example, resistance measurements require the flow of electric current through the tissues or blood being measured. Some transducers generate a small amount of heat due to the current flow. In most cases, this energy level is so low that its effect is insignificant. However, in dealing with living cells, care must continually be taken to avoid the possibility of energy concentrations that might damage cells or affect the measurements. Safety Considerations The methods employed in measuring variables in a living human subject must in no way endanger the life or normal functioning of the subject. Recent emphasis on hospital safety requires that extra caution must be taken in the design of any measurement system to protect the patient. Similarly, the measurement should not cause undue pain, trauma, or discomfort, unless it becomes necessary to endure these conditions in order to save the patient's life. BIO-MEDICAL INSTRUMENTATION (UEI608) Lecture: Resting and action potentials By Dr. Deepti Mittal (Associate Professor) Department of Electrical & Instrumentation Engineering Thapar Institute of Engineering & Technology Patiala, India RESTING AND ACTION POTENTIALS Certain types of cells within the body, such as nerve and muscle cells, are encased in a semipermeable membrane that permits some substances to pass through the membrane while others Neitherare kept the out.structure of the membrane nor the mechanism by which its permeability is exact controlled is known, but the substances involved have been identified by experimentation. Surrounding the cells of the body are the body fluids. These fluids are conductive solutions containing charged atoms known as ions. The principal ions are sodium (Na+), potassium (K+), and chloride (C-). The membrane of cells readily permits entry of potassium and chloride ions but effectively blocks the entry of sodium ions. Since the various ions seek a balance between the inside of the cell and the outside, both according to concentration and electric charge, the inability of the sodium to penetrate the membrane results in twothe First, conditions. concentration of sodium ions inside the cell becomes much lower than in the intercellular fluid outside. Excitable tissues - neuron (nerve tissue) - muscle fiber (muscle tissue) Neuron - primary structural and functional unit of nerve tissue (brain, spinal cord, nerves, sensory cells) - 4 – 130 μm dendrite axon terminal node of soma Ranvier axon hillock Schwann cell initial segment myelin sheath nucleus  Propagation of neuronal excitation from dendrites to the axon dendrites soma axon with an axon collateral Since the sodium ions are positive, this would tend to make the outside of the cell more positive than the inside. Second, in an attempt to balance the electric charge, additional potassium ions, which are also positive, enter the cell, causing a higher concentration of potassium on the inside than on the outside. This charge balance cannot be achieved, however, because of the concentration imbalance of potassium ions. Equilibrium is reached with a potential difference across the membrane, negative on the inside and positive on the outside. This membrane potential is called the resting potential of the cell and is maintained until some kind of disturbance upsets the equilibrium. Since measurement of the membrane potential is generally made from inside the cell with respect to the body fluids, the resting potential of a cell is given as negative. Research investigators have reported measuring membrane potentials in various cells ranging from - 60 to - 100 mV. Figure illustrates in simplified form the cross section of a cell with its resting potential. A cell in the resting state is said to be polarized. Polarized cell with its resting potential. Figure 48.7 Key Na K Sodium- potassium pump OUTSIDE OF CELL Potassium channel Sodium channel INSIDE OF CELL When a section of the cell membrane is excited by the flow of ionic current or by some form of externally applied energy, the membrane changes its characteristics and begins to allow some of the sodium ions to enter. This movement of sodium ions into the cell constitutes an ionic current flow that further reduces the barrier of the membrane to sodium ions. The net result is an avalanche effect in which sodium ions literally rush into the cell to try to reach a balance with the ions outside. At the same time potassium ions, which were in higher concentration inside the cell during the resting state, try to leave the cell but are unable to move as rapidly as the sodium ions. As a result, the cell has a slightly positive potential on the in- side due to the imbalance of potassium ions. This potential is known as the action potential and is approximately + 20 mV. A cell that has been excited and that displays an action potential is said to be depolarized; the process of changing from the resting state to the action potential is called depolarization. Figure shows the ionic movements associated with depolarization, and Figure illustrates the cross section of a depolarized cell. Depolarization of a cell. Na + ions Depolarized cell during an action potential rush into the cell while K+ ions attempt to leave. Once the rush of sodium ions through the cell membrane has stopped (a new state of equilibrium is reached), the ionic currents that lowered the barrier to sodium ions are no longer present and the membrane reverts back to its original, selectively permeable condition, wherein the passage of sodium ions from the outside to the inside of the cell is again blocked. Were this the only effect, however, it would take a long time for a resting potential to develop again. But such is not the case. By an active process, called a sodium pump, the sodium ions are quickly transported to the outside of the cell, and the cell again becomes polarized and assumes its resting potential. This process is called repolarization. Although little is known of the exact chemical steps involved in the sodium pump, it is quite generally believed that sodium is withdrawn against both charge and concentration gradients supported by some form of high-energy phosphate compound. The rate of pumping is directly proportional to the sodium concentration in the cell. It is also believed that the operation of this pump is linked with the influx of potassium into the cell, as if a cyclic process involving an exchange of sodium for potassium existed.  Key Na K  50 Membrane potential 0 (mV) Threshold  50 1 Resting potential  100 Time OUTSIDE OF CELL Sodium Potassium channel channel INSIDE OF CELL Inactivation loop 1 Resting state  Key Na K  50 Membrane potential 0 (mV) Threshold 2  50 1 2 Depolarization Resting potential  100 Time OUTSIDE OF CELL Sodium Potassium channel channel INSIDE OF CELL Inactivation loop 1 Resting state Figure 48.11-3 Key Na K 3 Rising phase of the action potential  50 Action Membrane potential potential 3 0 (mV) Threshold 2  50 1 2 Depolarization Resting potential  100 Time OUTSIDE OF CELL Sodium Potassium channel channel INSIDE OF CELL Inactivation loop 1 Resting state Figure 48.11-4 Key Na K 4 Falling phase of the action potential 3 Rising phase of the action potential  50 Action Membrane potential potential 3 0 (mV) Threshold 4 2  50 1 2 Depolarization Resting potential  100 Time OUTSIDE OF CELL Sodium Potassium channel channel INSIDE OF CELL Inactivation loop 1 Resting state Figure 48.11-5 Key Na K 4 Falling phase of the action potential 3 Rising phase of the action potential  50 Action Membrane potential potential 3 0 (mV) Threshold 4 2  50 1 5 1 2 Depolarization Resting potential  100 Time OUTSIDE OF CELL Sodium Potassium channel channel INSIDE OF CELL Inactivation loop 1 Resting state 5 Undershoot Figure 48.11a  50 Action potential Membrane potential 3 0 (mV) 2 4 Threshold  50 1 1 5 Resting potential  100 Time Waveform of the action potential. (Time scale varies with type of cell.) Figure shows a typical action-potential waveform, beginning at the resting potential, depolarizing, and returning to the resting potential after repolarization. The time scale for the action potential depends on the type of cell producing the potential. In nerve and muscle cells, repolarization occurs so rapidly following depolarization that the action potential appears as a spike of as little as 1 msec total duration. Heart muscle, on the other hand, repolarizes much more slowly, with the action potential for heart muscle usually lasting from 150 to 300 msec. Regardless of the method by which a cell is excited or the intensity of the stimulus (provided it is sufficient to activate the cell), the action potential is always the same for any given cell. This is known as the all-or-nothing law. The net height of the action potential is defined as the difference between the potential of the depolarized membrane at the peak of the action potential and the resting potential. Following the generation of an action potential, there is a brief period of time during which the cell cannot respond to any new stimulus. This period, called the absolute refractory period, lasts about 1 msec in nerve cells. Following the absolute refractory period, there occurs a relative refractory period, during which another action potential can be triggered, but a much stronger stimulation is required In nerve cells, the relative refractory period lasts several milliseconds. These refractory periods are believed to be the result of after-potentials that follow an action potential. Action Potential PROPAGATION OF ACTION POTENTIALS When a cell is excited and generates an action potential ionic currents begin to flow. This process can, in turn, excite neighboring cells or adjacent areas of the same cell. In the case of a nerve cell with a long fiber, the action potential is generated over a very small segment of the fiber's length but is propagated in both directions from the original point of excitation. In nature, nerve cells are excited only near their “input end”. As the action potential travels down the fiber, it cannot re-excite the portion of the fiber immediately upstream, because of the refractory period that follows the action potential. The rate at which an action potential moves down a fiber or is propagated from cell to cell is called the propagation rate. In nerve fibers the propagation rate is also called the nerve conduction rate, or conduction velocity. This velocity varies widely, depending on the type and diameter of the nerve fiber. The usual velocity range in nerves is from 20 to 140 meters per second (m/sec). Propagation through heart muscle is slower, with an average rate from 0.2 to 0.4 m/sec. Special time-delay fibers between the atria and ventricles of the heart cause action potentials to propagate at an even slower rate, 0.03 to 0.05 m/sec.  Action potential o Action potentials are brief, rapid, large, propogatory changes in membrane potentials produced by application of adequate stimulus to an excitable tissue. oAction potential = “impulse” oChanges during AP – Depolarization followed by repolarization of membrane Figure 48.9 TECHNIQUE Microelectrode Voltage recorder Reference electrode  Recording ati CRO electrode +40 stimulat Repolar Membrane potential on Depolariz +20 or 0 - iz a 20 on - ti 40 - 60 - (mV) 80 1 msec Time ( msecs. ) BIO-MEDICAL INSTRUMENTATION (UEI608) Lecture: Propagation of action potentials By Dr. Deepti Mittal (Associate Professor) Department of Electrical & Instrumentation Engineering Thapar Institute of Engineering & Technology Patiala, India  5. During the undershoot, membrane permeability to K+ is at first higher than at rest, then voltage-gated K+ channels close and resting potential is restored © 2011 Pearson Education, Inc.  During the refractory period after an action potential, a second action potential cannot be initiated The refractory period is a result of a temporary inactivation of the Na+ channels Conduction of Action Potentials At the site where the action potential is generated, usually the axon hillock, an electrical current depolarizes the neighboring region of the axon membrane Action potentials travel in only one direction: toward the synaptic terminals  Inactivated Na+ channels behind the zone of depolarization prevent the action potential from traveling backwards Figure 48.12-1 Axon Action Plasma potential membrane 1 Na Cytosol Figure 48.12-2 Axon Action Plasma potential membrane 1 Na Cytosol Action K potential 2 Na K BIO-MEDICAL INSTRUMENTATION (UEI608) Lecture: Bioelectric potentials By Dr. Deepti Mittal (Associate Professor) Department of Electrical & Instrumentation Engineering Thapar Institute of Engineering & Technology Patiala, India END